Genetic Variant CD247:c.429+2527T>G (chr1-167430497-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000700105.1(CD247):c.429+2527T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 394,626 control chromosomes in the GnomAD database, including 28,781 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10630 hom., cov: 33)

Exomes 𝑓: 0.38 ( 18151 hom. )

Consequence

CD247
ENST00000700105.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.787

Publications

10 publications found

Variant links:

Genes affected

CD247 (HGNC:1677): (CD247 molecule) The protein encoded by this gene is T-cell receptor zeta, which together with T-cell receptor alpha/beta and gamma/delta heterodimers, and with CD3-gamma, -delta and -epsilon, forms the T-cell receptor-CD3 complex. The zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. Low expression of the antigen results in impaired immune response. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CD247 Gene-Disease associations (from GenCC):

immunodeficiency 25
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CD247 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD247	NM_198053.3 link	c.*1184T>G		downstream_gene_variant		ENST00000362089.10	NP_932170.1	P20963-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD247	ENST00000362089.10 link	c.*1184T>G		downstream_gene_variant		1	NM_198053.3	ENSP00000354782.5		P20963-1

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55995

AN:

152102

Hom.:

10608

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.350

GnomAD4 exome

AF:

0.382

AC:

92698

AN:

242406

Hom.:

18151

AF XY:

0.382

AC XY:

46916

AN XY:

122876

show subpopulations

African (AFR)

AF:

0.302

AC:

2145

AN:

7112

American (AMR)

AF:

0.523

AC:

3826

AN:

7318

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

2941

AN:

9148

East Asian (EAS)

AF:

0.455

AC:

10328

AN:

22698

South Asian (SAS)

AF:

0.481

AC:

1039

AN:

2158

European-Finnish (FIN)

AF:

0.472

AC:

9664

AN:

20466

Middle Eastern (MID)

AF:

0.293

AC:

373

AN:

1272

European-Non Finnish (NFE)

AF:

0.361

AC:

56322

AN:

156070

Other (OTH)

AF:

0.375

AC:

6060

AN:

16164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2779

5558

8336

11115

13894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

266

532

798

1064

1330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.368

AC:

56060

AN:

152220

Hom.:

10630

Cov.:

AF XY:

0.379

AC XY:

28216

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.301

AC:

12516

AN:

41526

American (AMR)

AF:

0.470

AC:

7185

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1054

AN:

3472

East Asian (EAS)

AF:

0.429

AC:

2216

AN:

5162

South Asian (SAS)

AF:

0.455

AC:

2192

AN:

4822

European-Finnish (FIN)

AF:

0.484

AC:

5143

AN:

10620

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.361

AC:

24519

AN:

68000

Other (OTH)

AF:

0.351

AC:

741

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1864

3728

5593

7457

9321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.365

Hom.:

36114

Bravo

AF:

0.368

Asia WGS

AF:

0.412

AC:

1433

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.47

(source)

DANN

Benign

0.67

PhyloP100

-0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over